Longitudinal analysis of sociodemographic, clinical and therapeutic factors of HIV-infected individuals in Kinshasa at antiretroviral therapy initiation during 2006-2017

Background The benefits of antiretroviral therapy (ART) underpin the recommendations for the early detection of HIV infection and ART initiation. Late initiation (LI) of antiretroviral therapy compromises the benefits of ART both individually and in the community. Indeed, it promotes the transmission of infection and higher HIV-related morbidity and mortality with complicated and costly clinical management. This study aims to analyze the evolutionary trends in the median CD4 count, the median time to initiation of ART, the proportion of patients with advanced HIV disease at the initiation of ART between 2006 and 2017 and their factors. Methods and findings HIV-positive adults (≥ 16 years old) who initiated ART between January 1, 2006 and December 31, 2017 in 25 HIV care facilities in Kinshasa, the capital of DRC, were eligible. The data were processed anonymously. LI is defined as CD4≤350 cells/μl and/or WHO clinical stage III or IV and advanced HIV disease (AHD), as CD4≤200 cells/μl and/or stage WHO clinic IV. Factors associated with advanced HIV disease at ART initiation were analyzed, irrespective of year of enrollment in HIV care, using logistic regression models. A total of 7278 patients (55% admitted after 2013) with an average age of 40.9 years were included. The majority were composed of women (71%), highly educated women (68%) and married or widowed women (61%). The median CD4 was 213 cells/μl, 76.7% of patients had CD4≤350 cells/μl, 46.1% had CD4≤200 cells/μl, and 59% of patients were at WHO clinical stages 3 or 4. Men had a more advanced clinical stage (p <0.046) and immunosuppression (p<0.0007) than women. Overall, 70% of patients started ART late, and 25% had AHD. Between 2006 and 2017, the median CD4 count increased from 190 cells/μl to 331 cells/μl (p<0.0001), and the proportions of patients with LI and AHD decreased from 76% to 47% (p< 0.0001) and from 18.7% to 8.9% (p<0.0001), respectively. The median time to initiation of ART after screening for HIV infection decreased from 40 to zero months (p<0.0001), and the proportion of time to initiation of ART in the month increased from 39 to 93.3% (p<0.0001) in the same period. The probability of LI of ART was higher in married couples (OR: 1.7; 95% CI: 1.3–2.3) (p<0.0007) and lower in patients with higher education (OR: 0.74; 95% CI: 0.64–0.86) (p<0.0001). Conclusion Despite increasingly rapid treatment, the proportions of LI and AHD remain high. New approaches to early detection, the first condition for early ART and a key to ending the HIV epidemic, such as home and work HIV testing, HIV self-testing and screening at the point of service, must be implemented.

Analytical challenges in estimating the effect of exposures that are bounded by follow-up time: experiences from the Blood Stream Infection—Focus on Outcomes study

Objective To illustrate the challenges of estimating the effect of an exposure that is bounded by duration of follow-up on all-cause 28-day mortality, whilst simultaneously addressing missing data and time-varying covariates. Study design and methods BSI-FOO is a multicentre cohort study with the primary aim of quantifying the effect of modifiable risk factors, including time to initiation of therapy, on all-cause 28-day mortality in patients with bloodstream infection. The primary analysis involved two Cox proportional hazard models, first one for non-modifiable risk factors and second one for modifiable risk factors, with a risk score calculated from the first model included as a covariate in the second model. Modifiable risk factors considered in this study were recorded daily for a maximum of 28 days after infection. Follow-up was split at daily intervals from day 0 to 28 with values of daily collected data updated at each interval (i.e., one row per patient per day). Analytical challenges Estimating the effect of time to initiation of treatment on survival is analytically challenging since only those who survive to time t can wait until time t to start treatment, introducing immortal time bias. Time-varying covariates representing cumulative counts were used for variables bounded by survival time e.g. the cumulative count of days before first receipt of treatment. Multiple imputation using chained equations was used to impute missing data, using conditional imputation to avoid imputing non-applicable data e.g. ward data after discharge. Conclusion Using time-varying covariates represented by cumulative counts within a one row per day per patient framework can reduce the risk of bias in effect estimates. The approach followed uses established methodology and is easily implemented in standard statistical packages.

Relationship Between Nutrition Intake and Outcome After Subarachnoid Hemorrhage: Results From the International Nutritional Survey

Background: A previous study suggested an association between low caloric intake(CI), negative nitrogen balance, and poor outcome after subarachnoid hemorrhage(SAH). Objective of this multinational, multicenter study was to investigate whether clinical outcomes vary by protein intake(PI) or CI in SAH patients adjusting for the nutritional risk as judged by the modified NUTrition Risk in the Critically Ill (mNUTRIC) score. Methods: The International Nutrition Survey(INS) 2007-2014 was utilized to describe the characteristics, outcomes and nutrition use. A subgroup of patients from 2013 and 2014(when NUTRIC score was captured) examined the association between CI and PI and time to discharge alive(TTDA) from hospital using Cox regression models, adjusting for nutrition risk classified by the mNUTRIC score as low(0-4) or high(5-9). Results: There were 489 SAH patients(57% female with a mean ± SD age 57.5 ± 13.9 years, BMI of 25.9 ± 5.3 kg/m2 and APACHE-2 score 19.4 ± 7.0. Majority(85%) received enteral nutrition(EN) only, with a time to initiation of EN of 35.4 ± 35.2 hours. 64% had EN interrupted. Patients received a CI of 14.6 ± 7.1 calories/kg/day and PI 0.7 ± 0.3 grams/kg/day corresponding to 59% and 55% of total prescribed CI and PI respectively. In the 2013 and 2014 subgroup there were 226 SAH patients with a mNUTRIC score of 3.4 ± 1.8. Increased CI and PI were associated with faster TTDA among high mNUTRIC patients(HR per 20% of prescription received = 1.34[95% CI,1.03 -1.76] for CI and 1.44[1.07 -1.93] for PI), but not low mNUTRIC patients(CI: HR = 0.95[0.77 -1.16] PI:0.95[0.78 -1.16]). Conclusions: Results from this multicenter study found that SAH patients received under 60% of their prescribed CI and PI. Further, achieving greater CI and PI in hi risk SAH patients was associated with improved TTDA. mNUTRIC serves to identify SAH patients that benefit most from artificial nutrition and efforts to optimize protein and caloric delivery in this subpopulation should be maximized.

Turnaround Time for Microbiological Testing of Tuberculosis in Routine Clinical Practice and Time to Patient Initiation on Treatment, Iganga Hospital, Uganda: 2012-2017

Background: Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis (Mtb) that is resistant to atleast isoniazid and rifampicin. Delayed diagnosis and treatment initiation lead to increased transmission and poor clinical outcomes. Although GeneXpert MTB/RIF detects Mtb and rifampicin resistance within 2 hours, the TB control program needs to understand the turnaround time (TAT) from specimen collection to treatment initiation and its impact on treatment outcomes for patients with Rif-resistant TB in Uganda. We quantified the TAT overall and at each step of the process for diagnosis of Rif-resistant TB in routine clinical practice and time to initiation on appropriate treatment over a 5-year period.Methods: We conducted a retrospective study in Iganga General Hospital, Eastern Uganda. Both Rif-resistant and MDR TB cases are recorded in the same register. We abstracted data from the MDR-TB clinic and laboratory registers (Form 2A and 096B) at Iganga Hospital, 2012-2017, including dates for smear microscopy, Xpert MTB/RIF, initiating MDR-TB patients on treatment after the Xpert MTB/RIF test, and dates for Drug Susceptibility Testing (DST). We performed descriptive and survival analysis to estimate the TAT for microbiological testing and time to initiation on treatment among MDR-TB patients.Results: Overall, we analyzed sixty-three (63) records, including specimens from Iganga Hospital patients and referrals from other health facilities. Of 63 records, 81% (51/63) had microscopy results, 97% (61/63) had Xpert MTB/RIF results, and 98% (62/63) had DST results. The median TAT for smear microscopy was the same day or within 1 day for 38/51 (75%) of the patients, ranging from 2-31 days for the rest. TAT for Xpert MTB/RIF results was the same day or within 1 day for 45/61 (75%), while the rest ranged from 2-183 days. Treatment initiation was within 28 days for 30/61 (50%). Reporting results for DST, took a median time of 13 days (IQR: 10-40 days) with an overall range of 0-334 days. Conclusion: Prompt Xpert MTB/RIF testing and result reporting allows timely treatment initiation. We recommend timely release of DST results by the National Tuberculosis Reference Laboratory or decentralization of DST services so as to mitigate delays and improve patient re-evaluation.